Reduced deformability of red blood cells (RBC, also known as erythrocyte), is a type of cellular injury. It has been identified as one of the causes of abnormal microcirculation. Several diseases, such as sickle cell anemia, diabetes mellitus and stroke, are also associated with impaired RBC deformability. It is known that ATP depletion or the flexibility of erythrocyte membranes can be reduced by calcium load. Besides, modification of lipid properties may also affect RBC deformability since the erythrocyte membrane includes a lipid bilayer.
Triacylglycerols (TG) are important constituents of blood. 1.7 m M/liter TG are normally present in the plasma of a healthy adult. Since TG are hydrophobic in nature, most of them are bound to lipoproteins when they are circulating in the bloodstream. They are hydrolyzed by lipase and the released free fatty acids are transported into the tissues. Lipid storage has been recognized as the main physiological function of TG. Few studies have been undertaken to investigate if TG has other biological activities. No one has previously evaluated the therapeutic application of a solution of TG as a pharmaceutical preparation which is either mixed with cells or injected into a mammalian body.
There are various kinds of fatty acids contained in triacylglycerols. For a naturally occuring TG, it is very rare to find the same fatty acid component in all three ester positions. In other words, nearly all naturally occuring TG are mixed TG.
Fatty acids are straight chain hydrocarbons that are either saturated or unsaturated. Unsaturated fatty acids contain double bonds while the saturated ones do not. Based on the degree of saturation, unsaturated fatty acids can be either monounsaturated or polyunsaturated. It is known that the fatty acid component contained in the lipids may influence the physical property as well as the biological activity of the lipids. For instance, in an article by M. F. Oliver "cigarette smoking, polyunsaturated fats, linoleic acid, and coronary heart disease" Lancet, 1989 Vol. 333, 1241, it was concluded that people with high risk of coronary artery disease should take more polyunsaturated fatty acids and particularly, those rich in linoleic acid. Another recent study, Lepran, et al., Journal of Cardiovascular Pharmacology 1992, Vol. 19, 40, showed that in rats fed with linoleic acid-rich diet, the occurrence of life-threatening arrhythmia was decreased both during the acute phase of myocardial ischemia and during the reperfusion. However, even though these studies claimed a beneficial effect of oleic acid-rich or linoleic acid-rich diet, the therapeutic application of a preparation containing triacylglycerols with fatty acids of either oleic acid or linoleic acid or others as the only type of esterified acid component has not been disclosed.
Reduced erythrocyte deformability is implicated in the pathogenesis of abnormal microcirculation of blood. It has also been reported that RBC deformability is reduced in patients undergoing cardiopulmonary bypass. Obstruction of microcirculation may cause tissue damage, such as ischemia and the infraction of brain, heart and kidney. These damages may lead to organ dysfunction and increase the morbidity as well as the mortality of the patients.
Presently, several other drugs such as pentoxyfylline, vinpocetin and piracetam are proposed for use in improving RBC deformability. However, these drugs are not suitable for cardiac patients undergoing cardiopulmonary bypass because they have other pharmacological activities and possible adverse effects on the cardiovascular system.
It is therefore an object of the present invention to provide a method of preserving RBC deformability of a mammalian body by using a pharmaceutical preparation.
It is another object of the present invention to provide a method of preserving and improving RBC deformability of a mammalian body by using a pharmaceutical preparation which does not have adverse pharmacological activities on the cardiovascular system.
It is a further object of the present invention to provide a method of improving RBC deformability of a mammalian body by using a pharmaceutical preparation which contains a substance that is normally found in the bloodstream of such mammalian body.
It is yet another object of the present invention to provide a method of preventing injury to cells and tissues of a mammalian body by treating such cells and tissues with a pharmaceutical preparation that does not adversely influence cardiovascular functions of the mammalian body.
It is still another object of the present invention to provide a method of preventing injury to cells and tissues of a mammalian body by introducing into the bloodstream of said body a pharmaceutical preparation that contains triacylglycerol in a pharmaceutically effective amount.